The objective of this investigation is to determine whether factors produced by neuronal and circulatory cells modulate the response be periodontal ligament (PDL) and alveolar bone cells to mechanical stress, particularly as it is applied during orthodontic tooth movement. The specific aims are to: 1) localize the neuropeptides substance P, vasoactive intestinal peptide, methionine-enkephalin, calcitonin gene- related peptide and the cytokines Interleukin 1 alpha, 1 beta, Interleukin 2, interferon-gamma and tumor necrosis factor-alpha; 2) assess the effects of each of these agents on an in vitro bone remodeling test system; 3) investigate whether these agents bind to target cells in the PDL upon local administration in vivo; and 4) determine whether specific antibodies, which bind to epitope sites that are common to the region of receptor attachment, are capable of inhibiting these agents in an in vitro bone remodeling system. Four experiments are planned. In the first, each agent will be localized by immunohistochemical staining in jaw sections of cats whose one maxillary canine would be translated distally for period of time ranging from 1h to 28d. In the second, each agent will be added to mouse calcaria cultures to study its direct effect on bone remodeling in vitro; or to cultures of PDL fibroblasts to determine whether stimulated fibroblasts produce factors which affect bone remodeling. In the third, agents will be injected directly into cat PDL in vivo and determinations will be made immunohistochemically and autoradiographically of the binding of each agent to PDL target cells. In the fourth, specific antibodies to each agent will be added to mouse calvaria cultures, together with each agent, in an attempt to inhibit the effects of these agents on bone remodeling in vitro. This project is aimed at increasing knowledge about the biochemical aspects of orthodontic tooth movement. Such information on the mode of action of specific products of nervous and inflammatory cells may lead to the development of new diagnostic and therapeutic means in orthodontics.